The integration of behavior and physiology is critical to human health;disease states can result when a person's actions are inappropriately regulated by his physiological state and vice versa. The relationship between food intake and digestive function illustrates this interdependence. The failure to respond behaviorally to satiety signals coming from the digestive tract can cause obesity, while many digestive diseases are caused by aberrant responses of the digestive tract to food. Together obesity and digestive disease affect a significant percentage of the U.S. population, with direct and indirect economic costs in the billions of dollars. The long-term goal of this research is to understand the genes and physiological pathways required for the regulation of digestion and feeding behavior in the fruit fly Drosophila melanogaster, an organism that has proven to be an excellent model system for studies of feeding regulation and energy balance and that continues to be a leading system for molecular genetic investigations. The specific focus of this project is on a Drosophila mutation, lot's wife (lwf), which disrupts normal food processing and causes the adult flies to die in less than 6 days. The mutation responsible for the lwf phenotype has been identified and lies in a gene that is a member of a gene family found in both flies and in humans, but the biological functions of the genes in this family are entirely unknown. The three aims of this project are designed to begin elucidating the function of the lwf gene by determining where the gene is expressed and exactly how its mutation alters food processing and feeding behavior. The experiments in specific aim 1 seek to confirm genetically the identity of the lwf gene while characterizing potential additional alleles of the gene. In specific aim 2, behavioral studies and quantitative analysis of food processing and distribution will be used to define more precisely the phenotype of the lwf mutant flies. Finally, the spatial distribution of lwf gene expression will be examined in specific aim 3. It is believed that analysis of the lwf mutation will yield new insights into the regulation of food processing and feeding behavior;furthermore, this mutant should prove to be an excellent starting point for future studies into the genetics of appetite regulation and digestive physiology. Digestive disease and obesity are major public health concerns that result from aberrant regulation of food intake and processing. In focusing on a mutation in the fruit fly Drosophila that affects digestion and feeding behavior, this project will provide insight into the function of the human digestive system and its role in appetite control.